Funds are requested for the purchase of a next generation, high-speed X-ray detector for the Southeast Regional Collaborative Access Team (SER-CAT) Sector 22, Advanced Photon Source, Argonne National Laboratory (www.ser-cat.org), as the Phase II optimization of 22ID. Organized in 1997, SER-CAT has grown to include over 90 research groups from 25 institutions spanning 14 states. The SER-CAT beam lines provide data and structures in support of (1) federally funded and other research activities, (2) industrial drug discovery and (3) preliminary results needed for new proposals. SER-CAT's success is reflected by the fact that its premiere beam line 22ID has become one of the world's most productive facilities for macromolecular crystallography. SER-CAT member institutions view SER-CAT to be critical to their structural biology programs and in attracting (and retaining) the best and brightest faculty and students. The fact that each institution must pay yearly dues (based on their share of capital expense) to maintain the facility and to receive beam time reflects the importance of SER-CAT to their programs. The aims of the proposed acquisition of a next generation, fast detector are: (1) the current detector in use on 22ID is now over five years old and nearing the point where reliability can become an issue. Thus, good management requires that SER-CAT be proactive in assuring its membership access to a reliable large format CCD detector on its premier beam line. (2) The current proposal represents Phase II of our planned optimization of data collection capability at SER-CAT. The proposed detector will maximize the impact of the Phase I microdiffractometer acquisition by improving the signal-to-nose ratio for data from weekly diffracting micro crystals that our members often find difficult to collect data from at SER-CAT. (3) The proposed Rayonix MX325-HS-100T detector (with its 0.097 sec readout) should double or triple the number of experiments that can be carried out per day on 22ID, which in-turn should increase the success of extramural funding (i.e. more projects get beam time producing more results). (4) The proposed detector will allow us to move the current MX300 detector on 22ID to the SER-CAT bending magnet beam line 22BM. This move will significantly increase the range of experiments that can be carried out on 22BM. importantly;the MX300 detector will serve as a needed backup for 22ID with the MAR 225 installed back on 22BM, in the event of 22ID detector failure. SER-CAT currently supports over 80 NIH funded research projects aimed at producing three-dimensional structures of proteins related to understanding protein structure-function relationships and their mechanism of action. These studies will significantly impact our knowledge of cellular processes and provide valuable insights into the molecular basis of disease that will lead to better therapeutics.